This application is a 371 of PCT/EP98/07364, filed on Nov. 17, 1998.
The present invention describes the use of cationic vinylidene, allenylidene and higher cumulenylidene complexes of ruthenium or osmium as catalysts or catalyst precursors for olefin metathesis reactions of all types. The present invention also relates to new cationic allenylidene complexes of ruthenium and osmium which can be used as metathesis catalysts with preferred embodiment. These catalysts or catalyst precursors are easy to prepare from well accessible, stable and essentially non toxic starting materials, can be isolated and stored, they exhibit a high catalytic activity, a good compatibility with functional groups, solvents, water and additives, and they need not to be activated by any additive. Olefins of all types can be used as the substrates in the present invention.
Olefin metathesis refers to the interchange of carbon atoms between a pair of double bonds. Reactions of this type have found applications to processes of industrial importance (Reviews: Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization, Academic Press, New York, 1997; Schuster, M. et al., Angew. Chem. 1997, 109, 2125). Olefin metathesis reactions are catalyzed by various metal compounds. Many of the classical catalysts consist of mixtures of various components, they are ill defined in their chemical composition, show a poor compatibility with functional groups and are inefficient as a consequence of little active species present. More modern catalysts or catalyst precursors with a better application profile comprise complexes of the general types I-IX: (references: type I (M=Ru, Os): WO 96/04289, 15.02.1996; Nguyen S. T. et al. J. Am. Chem. Soc. 1992, 114, 3974; Nguyen S. T. et al. J. Am. Chem. Soc. 1993, 115, 9858; Schwab, P. et al. Angew. Chem. 1995, 107, 2179 (Angew. Chem. Int. Ed. Engl., 1995, 34, 2039); Schwab, P. et al. J. Am. Chem. Soc. 1996, 118, 100; Mohr, B. et al. Organometallics 1996, 15, 4317; Wilhelm, T. E. et al. Organometallics 1997, 16, 3867; Belderrain, T. R. Organometallics 1997, 16, 4001. Type II (M=Mo, W): Schrock, R. R. et al. J. Am. Chem. Soc. 1990, 112, 3875; Fujimura, O. et al. Organometallics 1996, 15, 1865. Type III: Quignard, F. et al. J. Mol. Catal. 1986, 36, 13. Type IV (M=Nb, Ta): Rocklage, S. M. et al. J. Am. Chem. Soc. 1981, 103, 1440; Wallace, K. C. et al. Macromolecules 1987, 20, 448. Type V (cp=cyclopentadienyl or substituted cyclopentadienyl): U.S. Pat. No. 4,567,244, 28.01.1986. Type VI: Herrmann, W. A. et al. Angew. Chem. 1991, 103, 1704. Type VII: Nugent, W. A. et al. J. Am. Chem. Soc. 1995, 117, 8992. Type VII: Davie E. S. J. Catal. 1972, 24, 272. Type IX: Herrmann, W. A. et al. Angew. Chem. 1996, 108,1169.) 
A major disadvantage of these complexes relates to their preparation which requires either reagents which are hazardous (e. g. type I: diazoalkanes), or difficult to prepare (e.g. type I: diphenylcyclopropene), or extremely sensitive (e. g. type II, III, IV, V, VI). Another disadvantage relates to the fact that some of these metathesis catalysts themselves are very sensitive to oxygen, moisture and/or polar functional groups and must be handled with great care under a strictly inert athmosphere (e. g. types II, III, IV, V). Another disadvantage relates to the fact that some of these complexes exhibit a reasonable reactivity only after activation with an additive, which can either be hazardous (e. g. for type IX: diazoalkanes) or toxic (e. g. for type VII: PbEt4). Catalysts of type VI are active only when deposited on special oxidic supports. Therefore a stringent need for metathesis catalysts persists, which reach or surpass the activity of the best catalysts I-IX described to date, but which are more readily accessible, require no hazardous reagents for their preparation, are robust, easy to isolate and handle, and need not be activated by any hazardous or toxic additives.
The present invention, meets the criteria mentioned above. Surprisingly we find that cationic vinylidene, allenylidene and higher cumulenylidene complexes of ruthenium or osmium are highly efficient catalysts or catalyst precursors for olefin metathesis reactions of all types. These catalysts or catalyst precursors are easy to prepare from well accessible, stable and essentially non toxic starting materials, can be isolated and stored, they exhibit a high catalytic activity, a good compatibility with functional groups, solvents, water and additives, and they need not to be activated by any additive. Of the catalysts mentioned above, compounds of the general type XII, as specified below, are new compounds.
Specifically, the present invention relates to the use of vinylidene, allenylidene and higher cumulenylidene complexes of the general formula X as catalysts in olefin metathesis reactions of all types 
wherein
M is Ru or Os;
X can be selected from any anionic ligand;
L2 can be selected from any type of phosphine, sulfonated phosphine, fluorinated phosphine, functionalized phosphine bearing up to three aminoalkyl-, ammoniumalkyl-, alkoxyalkyl-, alkoxycarbonylalkyl-, hydroxycarbonylalkyl-, hydroxyalkyl-, ketoalkyl-groups, phosphite, phosphinite, phosphonite, arsine, stibene.
L1 can be selected from any neutral xcfx80-bond ligand, preferably arene, substituted arene, heteroarene, independent of whether they are mono- or polycyclic;
A, B can be independently selected from hydrogen or a hydrocarbon from the group consisting of C1-C20 alkyl, aryl, C2-C20 alkenyl, alkynyl, C1-C20 alkoxy, carboxylate, carbamate, C2-C20 alkenyloxy, alkynyloxy, aryloxy, alkoxycarbonyl, C1-C20 alkylthio, alkylsulfonyl, alkylsulfinyl, arylthio, arylsulfonyl, arylsulfinyl, alkylamido, alkylamino, each of which may be substituted with C1-C10 alkyl, perfluoroalkyl, aryl, alkoxy or with halogen;
Yxe2x88x92 may be selected from any non-coordinating anion;
n is 0-5;
in a preferred embodiment:
M is Ru or Os
X is halogen
L2 is selected among phosphines bearing one or more secondary alkyl, tertiary alkyl, or cycloalkyl groups, preferably P(isopropyl)3, P(cyclohexyl)3, P(cyclopentyl)3, P(neopentyl)3, P(tertiobutyl)3.
L1 is benzene or a substituted benzene derivative bearing up to six substituents which may be identical or not identical and can be independently selected from C1-C20 alkyl, aryl, alkoxy, aryloxy, alkylsulfonyl, arylsulfonyl, perfluoroalkyl, alkylthio, alkenylthio, C2-C10 alkenyl, alkynyl, alkenyloxy, alkynyloxy, or halogen, most preferably L1 is toluene, xylene, cymene, trimethylbenzene, tetramethylbenzene, hexamethylbenzene, tetraline, naphthalene, or polycyclic arenes and their derivatives.
Yxe2x88x92 is selected from PF6xe2x88x92, BF4xe2x88x92, BPh4xe2x88x92, F3CSO3xe2x88x92, H3CSO3xe2x88x92, ClO4xe2x88x92, SO4xe2x88x92, NO3xe2x88x92, PO4xe2x88x92, CF3COOxe2x88x92, B(C6F5)4xe2x88x92, RSO3xe2x88x92, RCOOxe2x88x92 with R being selected from C1-C20 alkyl, aryl
n is 1.
The most preferred catalysts of the present invention include XI 
wherein
L2 can be selected from P(isopropyl)3, P(cyclohexyl)3, P(cyclopentyl)3, P(neopentyl)3, P(tertiobutyl)3 
Yxe2x88x92 is selected from PF6xe2x88x92, BF4xe2x88x92, BPh4xe2x88x92, F3CSO3xe2x88x92, H3CSO3xe2x88x92, ClO4xe2x88x92, SO4xe2x88x92, NO3xe2x88x92, PO4xe2x88x92, CF3COOxe2x88x92, B(C6F5)4xe2x88x92, RSO3xe2x88x92, RCOOxe2x88x92 with R being selected from C1-C20 alkyl, aryl
The preparation of these catalysts can be achieved by following the approach described in: Pilette, D. et al., Organometallics 1992, 11, 809.
The present invention also relates to new compounds of the general type XII 
wherein
M is Ru or Os
X can be selected from any anionic ligand;
L1 can be selected from any neutral xcfx80-bond ligand, preferably arene, substituted arene, heteroarene, independent of whether they are mono- or polycyclic;
L2 is selected among phosphines, arsine or stibenes bearing one or more secondary alkyl, tertiary alkyl, or cycloalkyl groups;
A, B can be independently selected from hydrogen or a hydrocarbon from the group consisting of C1-C20 alkyl, aryl, C2-C20 alkenyl, alkynyl, C1-C20 alkoxy, carboxylate, carbamate, C2-C20 alkenyloxy, alkynyloxy, aryloxy, alkoxycarbonyl, C1-C20 alkylthio, alkylsulfonyl, alkylsulfinyl, arylthio, arylsulfonyl, arylsulfinyl, alkylamido, alkylamino, each of-which may be substituted with C1-C10 alkyl, perfluoroalkyl, aryl, alkoxy or with halogen;
Yxe2x88x92 may be selected from any non-coordinating anion.
Compounds of the general type XII can be used as catalysts for olefin metathesis reactions according to the present invention. In a preferred embodiment
M is Ru
X is halogen
L1 is benzene or substituted benzene
L2 is selected among phosphines, arsine or stibenes bearing one or more secondary alkyl, tertiary alkyl, or cycloalkyl groups
A, B can be independently selected from a hydrocarbon from the group consisting of C1-C20 alkyl, aryl,
Yxe2x88x92 may be selected from any non-coordinating anion.
Compounds of the general type XII can be used as most preferred catalysts for olefin metathesis reactions according to the present invention, wherein
M is Ru
X is chloride
L1 is p-cymene
L2 is selected among P(isopropyl)3, P(cyclohexyl)3, P(cyclopentyl)3, P(neopentyl)3, P(tertiobutyl)3.
A, B are aryl or substituted aryl
Yxe2x88x92 may be selected from PF6xe2x88x92, BF4xe2x88x92, BPh4xe2x88x92, F3CSO3xe2x88x92, H3CSO3xe2x88x92, ClO4xe2x88x92, SO4xe2x88x92, NO3xe2x88x92, PO4xe2x88x92, CF3COOxe2x88x92, B(C6F5)4xe2x88x92, RSO3xe2x88x92, RCOOxe2x88x92 with R being selected from C1-C20 alkyl, aryl.
The synthesis of compounds of the general type XII can be achieved according to Equation 1; examples for the preparation of compounds of the general type XII which serve as catalysts with most preferred embodiments according to the present invention are described in Examples 1 and 2. The ease of this preparation is a distinct advantage for the process of this invention over the processes of the prior art. Another major advantage relates to the fact that all hazardous, unstable and difficult to handle reagents are avoided which were previously used for the preparation of highly performing metathesis catalysts. This refers particularly to diazoalkanes and cyclopropene derivatives which are avoided in the catalysts used in the present invention. The fact that the cationic ruthenium or osmium complexes of the general type X-XII must not be activated by addition of diazoalkanes distinguishes them from other metathesis catalysts presently used, in particular from the cationic bisallylruthenium (+4) complexes of the general type IX previously described in the literature (Herrmann, W. A. et al. Angew. Chem. 1996, 108, 1169). 
Equation 1. Example for the synthesis of a compound of the general type XII which can serve as metathesis catalyst according to the present invention.
It is not necessary to isolate and purify the catalyst precursor, but cationic complexes of the general type X-XII outlined above may be prepared in situ and directly used in metathesis reactions.
Examples of the reactons induced by the catalysts mentioned above include, but are not limited to, the ring closing metathesis (RCM) of acyclic dienes and polyenes, the metathesis of enynes and dienynes, the ring opening metathesis polymerization (ROMP) of cyclic olefins, the acyclic diene metathesis polymerization (ADMET) of acyclic dienes or polyenes, the depolymerization of olefinic polymers, and the cross metathesis of two or more olefins. The present invention also applies to combinations of these types of metathetic reactions, to domino processes thereof (Tietze, L. F. et al. Angew. Chem. Int. Ed. Engl. 1993, 32, 131), and to the dimerization or oligomerization of dienes followed by subsequent ring closure (cyclodi[oligo]merization).
The present invention applies to all types of olefins, independent of whether they are cyclic oracyclic, strained or unstrained, as well as to mixtures of olefins. The substrates can be used in polymer supported form or can be successively added to the reaction mixture.
The reactions are usually carried out by contacting the olefin substrate (neat or in solution) with the catalyst and optionally heating the mixture until the reaction is complete. The temperatures can range from xe2x88x9220xc2x0 C. to about 150xc2x0 C., preferably 10xc2x0 C. to 90xc2x0 C. The reaction time is not critical and can be from a few minutes to several days. The reactions are generally carried out under inert atmosphere, most preferably nitrogen, argon or CO2, but the presence of oxygen may be tolerated under certain circumstances. The reaction can be carried out under irradiation of the reaction mixture e. g. by visible or UV-light, or by ultrasonic waves. The reaction can be performed in water or in the presence of water.
The ratio of catalyst to olefin substrate is not critical and can range from 1:5 to about 1:30000, preferably it is in the range of 1:20 to 1:2000.
Work-up of the reaction mixtures and purification is not critical and follows routine techniques depending on the specific properties of the products formed and/or the unreacted starting material. This may proceed either by distillation, filtration, chromatography, sublimation, crystallization, extraction as the preferred techniques.
Catalysts of the type described above are stable in the presence of a variety of functional groups, which include, but are not limited to, alcohol, acetal, ketal, keteneacetal, thiol, thioacetal, ketone, aldehyde, ester, ether, epoxide, gem-dialkyl group, amine, ammonium salt, amide, nitro, carboxylic acid, sulfide, disulfide, carbonate, carbamate, isocyanide, nitrile, urethane, urea, halogen, mine, sulfonate, sulfone, sulfoxide, silyl, stannyl, perfluoroalkyl, phosphonate, ferrocene, as well as oxygen-, nitrogen-, sulfur or phosphorous containing heterocycles.
In the case of ROMP, the present invention applies to the preparation of Vestenamer(copyright) (Drxc3xa4xler, A. et al. Der Lichtbogen 1986, 35, 24) and Norsorex(copyright) (Ohm, R. F.; Chemtech 1980, 183).
In the case of oligomerization and polymerization reaction of appropriate monomers, the propagating carbene moiety was found to be stable and continues to polymerize additional aliquots of monomer for a period after the original amount of monomer has been consumed. The added monomer may be identical or not identical to the original one.
In case of RCM, the catalysts mentioned above apply to the formation of all ring sizes xxe2x89xa75, including medium sized (8xe2x89xa6xxe2x89xa611) and large (xxe2x89xa712) rings, independent of whether the rings are carbocyclic or heterocyclic; the newly formed ring may be anellated to one or more pre-existing aromatic or non-aromatic carbo- or heterocyclic rings. The invention applies, but is not restricted, to the synthesis of products which may be used as pheromones, crown ethers, antibiotics, agro chemicals, pharmaceuticals for human and veterinary medicine, fragrances, flavors, perfume ingredients. Representative examples are compiled in Table 1.
In the case of the formation of macrocyclic rings which serve as perfume ingredients, the present invention applies to the synthesis of pentadecanolide or homologues, Arova 16 or homologues, civetone or homologues, muscenone or homologues, Exalton or homologues, muscenone or homologues, ethylenebrassylate (Musk 144) or homologues, and related macrocycles as described in Fxc3xcrstner, A. et al., Synthesis 1997, 792 and U.S. application Ser. No. 08/767,561 (16.12.1996).
In the case of the formation of medium or macrocyclic rings by RCM, the olefin substrates may be devoid of any conformational predisposition to ring closure as induced by various elements of structural preorganization.
Metathesis reactions catalyzed by the cationic vinylidene, allenylidene and higher cumulenylidene complexes of the general formula X-XII can be performed in any solvent or solvent mixture which does not inactivate the catalyst. This includes protic and aqueous solvents, compressed carbon dioxide (DE-A 19720798.7 (15.5.1997)), or perfluoroalkanes. However it is preferred to work under aprotic conditions in solvents with low coordination ability. Examples of preferred solvents include, but are not restricted to, dichloromethane, trichloromethane, 1,2-dichloroethane, trichloroethane, benzene, toluene, xylene, halobenzenes, cymene, tetrahydrofuran, diethylether, tert-butylmethylether, dimethoxyethane, petrol ether, hexane, cyclohexane, acetone. Depending on the specific physical properties of the substrates and products, the reactions can also be carried out with neat alkenes without any additional solvent added to the reaction mixture. Examples of cyclization reactions in preferred embodiments are given in Tables 1 and 2.
The concentration of the substrate (molarity, M) in a given solvent may be largely varied. Under certain circumstances the reaction can be carried out with neat substrates without any additional solvent. In the case of RCM leading to the formation of medium and macrocyclic rings it is preferred to work at molarities Mxe2x89xa60.1 in order to suppress the dimerization, cyclodimerization or polymerization of the diene substrates. In a preferred embodiment, solutions of the substrate and of the catalyst are combined at such a rate that the propensity of cyclization of the respective substrate is greater than that of a reactive encounter of two substrate molecules.
As a result of their stability in the presence of functional groups, the catalysts may be employed in the presence of one or more additives. Examples include, but are not limited to, metal salts, metal alkoxides, Lewis acids, perfluoroalkanes, phosphorous compounds, detergents, surfactants, silica, alumina, graphite, CaCO3, or aluminum powder.